Vgamma1+ T cells and tumor necrosis factor-alpha in ozone-induced airway hyperresponsiveness.
gammadelta T cells regulate airway reactivity, but their role in ozone (O3)-induced airway hyperresponsiveness (AHR) is not known. Our objective was to determine the role of gammadelta T cells in O3-induced AHR. Different strains of mice, including those that were genetically manipulated or antibody-depleted to render them deficient in total gammadelta T cells or specific subsets of gammadelta T cells, were exposed to 2.0 ppm of O3 for 3 hours. Airway reactivity to inhaled methacholine, airway inflammation, and epithelial cell damage were monitored. Exposure of C57BL/6 mice to O3 resulted in a transient increase in airway reactivity, neutrophilia, and increased numbers of epithelial cells in the lavage fluid. TCR-delta(-/-) mice did not develop AHR, although they exhibited an increase in neutrophils and epithelial cells in the lavage fluid. Similarly, depletion of gammadelta T cells in wild-type mice suppressed O3-induced AHR without influencing airway inflammation or epithelial damage. Depletion of Vgamma1+, but not of Vgamma4+ T cells, reduced O3-induced AHR, and transfer of total gammadelta T cells or Vgamma1+ T cells to TCR-delta(-/-) mice restored AHR. After transfer of Vgamma1+ cells to TCR-delta(-/-) mice, restoration of AHR after O3 exposure was blocked by anti-TNF-alpha. However, AHR could be restored in TCR-delta(-/-)mice by transfer of gammadelta T cells from TNF-alpha-deficient mice, indicating that another cell type was the source of TNF-alpha. These results demonstrate that TNF-alpha and activation of Vgamma1+ gammadelta T cells are required for the development of AHR after O3 exposure.
Matsubara
Shigeki
S
Division of Cell Biology, Department of Pediatrics, National Jewish Health and the University of Colorado Health Sciences Center, Denver, Colorado, USA.
Takeda
Katsuyuki
K
Jin
Niyun
N
Okamoto
Masakazu
M
Matsuda
Hiroyuki
H
Shiraishi
Yoshiki
Y
Park
Jung Won
JW
McConville
Glen
G
Joetham
Anthony
A
O'Brien
Rebecca L
RL
Dakhama
Azzeddine
A
Born
Willi K
WK
Gelfand
Erwin W
EW
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002452:Cell Count; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010126:Ozone; D011014:Pneumonia / Q000150:complications / Q000276:immunology / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000378:metabolism*
D000906:Antibodies; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone